This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. All cells respond environmental fluctuations by altering patterns of gene expression. Gene regulation in eukaryotes begins at initiation of transcription and continues through export and translation of messenger RNAs. In the yeast Saccharomyces cerevisiae, starvation for amino acids generates a signal leading to an increase in Gcn4p, a transcriptional activator protein. Gcn4p regulates over 500 genes, including those involved in amino acid biosynthesis. Thus, yeast cells that cannot obtain amino acids from their environment produce their own. Mechanisms of gene activation by Gcn4p have been well studied, but it is not clear how these genes are repressed after starvation conditions are relieved. Gcn4p requires the CCR4-NOT co-activator complex for full target gene expression. However, CCR4-NOT also possesses activities for the destruction of mRNAs. Our recent results indicate that CCR4-NOT plays in regulating genes under Gcn4p control after transcription. The goal of this research is to determine the exact post-transcriptional role(s) of CCR4-NOT in Gcn4p target gene expression.